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Gene regulator starts immune response

Jun 21, 2004

Researchers at UT Southwestern have identified several new components that help activate the immune system's T cells, findings that could lead to novel drug targets for treating leukemia and lymphomas.

T cells are the "foot soldiers" that fight infection and diseases in higher organisms, including humans. They contribute to the immune system by activating or suppressing certain cells and directly contacting and destroying infected cells.

In their research, published in the May 7 issue of Molecular Cell, Dr. Zhijian "James" Chen, associate professor of molecular biology and senior author of the study, and his colleagues identified new components in the signaling pathway, which is a series of chemical reactions that activate T cells.

"For the first time, we have demonstrated that we can replicate the T-cell signaling pathway in the test tube," Dr. Chen said.

During their experiments, the researchers uncovered a new series of reactions mediated by certain protein enzymes. These reactions trigger a master gene regulator called NF-kB, which plays a pivotal role in inflammation, immunity and cancer. The regulator's dysfunction in the immune system is a major culprit in several forms of leukemia and lymphoma, both cancers of the blood system.

Another finding is that a small protein called ubiquitin has important regulatory functions in the immune system independent of its best-known function - targeting other proteins for destruction.

"T cells have always been at the center of immunology, so it is quite exciting to find out that ubiquitin activation of protein kinases is a crucial mechanism for T-cell activation," said Dr. Lijun Sun, postdoctoral researcher in molecular biology and lead author of the study.

The next step is to determine whether the mechanism of ubiquitin activation of these proteins can be extended to other signaling systems beyond immunology. Also, researchers will see if the new components identified in the T-cell signaling pathway can serve as therapeutic targets for the treatment of human diseases such as lymphomas, said Dr. Chen.